Spontaneous contrast is theterm used to describe the echocardiographic appearance of smoke-like reflectances in intracardiac blood. Similar echoes can be seen in the blood of peripheral vessels. Although the prevalence of cardiac spontaneous contrast in a hospital-based echo lab is approximately 10%, contrast in peripheral vessels occurs in 80% of hospitalized patients. Furthermore, the targets are significantly larger and brighter in patients with coronary artery disease, cerebrovascular disease or cancer, compared to normals. The origin of these echoes is unknown. The hypothesis to be tested in this study is that contrast represents circulating cell aggregates, consisting of platelets and/or neutrophils. Using a canine model of spontaneous contrast, the specific aims are: 1) to define the relationship between microscopic evidence of platelet, white cell and red cell aggregates and spontaneous contrast; 2) to determine the role, if any, of rheologically important variables, including hematocrit, whole blood and plasma viscosity, plasma proteins, and sedimentation rate in the production of spontaneous contrast; 3) to quantitate the amount of contrast detected by echo with computerized image processing and correlate this with aggregate number and size or specific rheologic abnormalities; and 4) to determine the relationship between intracardiac and peripheral contrast. If circulating cell aggregates can be identified by non- invasive testing, the response to appropriate therapy can be followed non-invasively. The longterm objectives of this research are to determine the etiology of spontaneous contrast in humans, and to explore the diagnostic, prognostic and therapeutic implications of the apparent ubiquity of this finding in patients for whom arterial and venous thrombosis is a common complication. The eradication of this ultrasonic abnormality may produce therapeutic responses that have been heretofore unattainable without such a guide to drug response.